Non-compartment model to compartment model pharmacokinetics transformation meta-analysis – a multivariate nonlinear mixed model

Wang et al. BMC Systems Biology 2010, 4(Suppl 1):S8 http://www.biomedcentral.com/1752-0509/4/S1/S8

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Non-compartment model to compartment model pharmacokinetics transformation meta-analysis – a multivariate nonlinear mixed model Zhiping Wang1†, Seongho Kim1†, Sara K Quinney1, Jihao Zhou2, Lang Li1* From The ISIBM International Joint Conferences on Bioinformatics, Systems Biology and Intelligent Computing (IJCBS) Shanghai, China. 3-8 August 2009

Abstract Background: To fulfill the model based drug development, the very first step is usually a model establishment from published literatures. Pharmacokinetics model is the central piece of model based drug development. This paper proposed an important approach to transform published non-compartment model pharmacokinetics (PK) parameters into compartment model PK parameters. This meta-analysis was performed with a multivariate nonlinear mixed model. A conditional first-order linearization approach was developed for statistical estimation and inference. Results: Using MDZ as an example, we showed that this approach successfully transformed 6 non-compartment model PK parameters from 10 publications into 5 compartment model PK parameters. In simulation studies, we showed that this multivariate nonlinear mixed model had little relative bias (